Translocation of amino acyl residues from the membrane interface to the hydrophobic core: thermodynamic model and experimental analysis using ATR-FTIR spectroscopy.

The interactions of a series of histidine-containing peptides with biological model membranes have been investigated by attenuated total reflection Fourier transform infra red (ATR-FTIR) spectroscopy. Related peptides have previously been shown to exhibit antibiotic and DNA transfection activities. The 26-residue LAH4X4 peptides were designed in such a manner to form amphipathic helical structures in membrane environments. Four histidines and four variable amino acids X constitute one face of the helix whereas leucines and alanines characterize the opposite hydrophobic surface. The dichroic ratio of ATR-FTIR spectra has been used to follow the pH-dependent transition from in-plane to transmembrane alignments upon increase in pH. A theoretical model of the topological modulations is presented and the experimental transition curves analysed in order to reveal the Gibbs free energy of transition. The novel concept provides access to the free energy changes associated with the amino acids X incorporated into an extended alpha-helix and in the context of phospholipid bilayers. For the peptides of the series the Gibbs free energies associated with the transition from the membrane interface to the bilayer interior follow the sequence of amino acids: L<A approximately I<S approximately F<T approximately G<V approximately W<<Y.